title: Anxiety-like behaviors and expression of SERT and TPH in the dorsal raphé of estrogen- and fluoxetine-treated ovariectomized rats.
abstract: The anxiolytic effect of fluoxetine (Flx) was often ineffective in postmenopausal and estrogen-deficient patients, but such effect had not been experimentally demonstrated, particularly in the female rat model of estrogen deficiency. Here we determined the anxiety-like behaviors in ovariectomized (Ovx) rats treated for 4weeks with 10μg/kg 17β-estradiol s.c. (Ovx+E2), 10mg/kg Flx p.o. (Ovx+Flx) or a combination of both (Ovx+E2+Flx). Since Flx is known to induce anxiolysis in males, we first evaluated the Flx regimen in male rats. The results showed that anxiety-like behaviors were reduced in Flx-treated male rats. In contrast, Ovx+Flx rats still exhibited the same anxiety-like behaviors as in Ovx rats. Both Ovx+E2 and Ovx+E2+Flx rats, however, showed comparable reductions in anxiety-like behaviors, suggesting that Flx had no anxiolytic-like effect. Furthermore, E2 and E2+Flx similarly upregulated the mRNA expression of serotonin reuptake transporter (SERT) and tryptophan hydroxylase-2 in the dorsal raphé of Ovx rats, while having no effect on SERT expression in the frontal cortex, hippocampus, septum, amygdala and periaqueductal gray. In conclusion, Flx induced anxiolytic-like action in male rats. In Ovx rats, it was E2 and not Flx that exerted the anxiolytic-like action, which was mediated, in part, by altering serotonin metabolism in the dorsal raphé.
authors.affiliation: Physiology Division, Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani 12120, Thailand. pjantari@tu.ac.th
authors.forename: Jantarima
authors.initials: J
authors.lastname: Charoenphandhu
authors.forename: Jarinthorn
authors.initials: J
authors.lastname: Teerapornpuntakit
authors.forename: Amporn
authors.initials: A
authors.lastname: Nuntapornsak
authors.forename: Nateetip
authors.initials: N
authors.lastname: Krishnamra
authors.forename: Narattaphol
authors.initials: N
authors.lastname: Charoenphandhu
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D011903:Raphe Nuclei / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D017931:DNA Primers; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C482440:Sert1 protein, rat; D005473:Fluoxetine; D004958:Estradiol; D014365:Tryptophan Hydroxylase; C504569:tph2 protein, rat